The Art of Clinical Supply Planning : Quality Product in the Right Place at the Right Time

Transcription

1 The Art of Clinical Supply Planning : Quality Product in the Right Place at the Right Time Clinical Trial Supply Southeast 2015 July 15 th July 16 th RTP, North Carolina Presenters: Eva Allen Heather Phillips Grifols Clinical Trial Materials 1

2 AGENDA Grifols: The Company The Art of Clinical Supply Planning: Quality Product in the Right Place at the Right Time Example studies that highlight clinical supplies packaging, labeling, and IWRS solutions to complex protocol challenges for biological products including: Flexible Subject Location Dosing Home Healthcare Infusions Global Flexible Ancillary Supplies Electronic Drug Accountability Short Expiry Date Management Question and Answer 2

3 GRIFOLS: The Company Three Grifols divisions develop, produce, and distribute healthcare products worldwide. 1. BIOSCIENCE: Plasma-derived therapies 2. DIAGNOTICS: In vitro diagnostics, analyzers, reagents 3. HOSPITAL: Hospital logistics, IV solutions, medical devices Grifols BIOSCIENCE has a strong portfolio of plasma therapies to treat rare, chronic, and life-threatening conditions in multiple therapeutic areas:» Pulmonology» Hematology» Immunology» Neurology» Infectious disease» Shock and trauma Three BIOSCIENCE Manufacturing Facilities:» Barcelona, Spain» Los Angeles, California» Clayton, North Carolina 3

4 The Art of Clinical Supply Planning : Quality Product in the Right Place at the Right Time Packaging and Labeling IWRS Programming Distribution Setup Regulatory Submission and Approval Pharmacy and Monitor Training FPFV Startup Protocol Design And Forecast Administration and Supplies Investigational Medicinal Product 4

5 Investigational Medicinal Product Investigational Medicinal Product Developmental or Commercial Product Placebo or Comparators Expiry Dating Formulation, Vial Size Temperature Requirements Do Manufacturing Release Specifications Need to be Developed 5

6 Administration and Ancillary Supplies Administration and Supplies Route of Administration Where is IP Administered Supplies for Administration or Blinding Site or Sponsor Supplied Regional Specifications Labeling Requirements 6

7 Protocol Design and IMP Forecast Protocol Design And Forecast Forecasting for Manufacturing Blinded or Open Label Placebo Controlled Dose and Number of Infusions Number of Subjects Number of Countries and Depots Subject Enrollment Rates Study Duration Estimates Lot Size Overage 7

8 IWRS Programing IWRS Programming IWRS or Manual Process IWRS Vendor Selection IWRS Design Build Subject Management Supplies Management Reporting/Communication IWRS UAT and Go Live IWRS Manual and Training 8

9 Packaging and Labeling Packaging and Labeling Labeling Text Development/Regulations Pooled Drug Supply Blinded or Open Label Kit Optimize Kit Design for Cold Chain Distribution In-House Packing or Outsource Single Panel or Booklet Labels First SIV Target Date Packaging Lead Time Quality and EU QP Release Cost and Budget 9

10 Distribution Supply Chain Distribution Setup What Global Depots are Required Full Service Distribution Only In-House or Outsource Distribution Instructions Cold Chain Temperature Tracking Cost and Budget Considerations 10

11 Regulatory Submissions and Approvals Regulatory Submission and Approval CMC Documents for RA Submission Label Text Plans for Expiry Extensions Ancillary Supply Details QP Declarations Import License Process Forecast per Country Per Shipment or Total Quantity Timelines for Regulatory Approvals 11

12 Pharmacy / Monitor Training / Site Startup Pharmacy/ Monitor Training/ Site Startup Pharmacy Manual Development Drug Details Packaging Plan Distribution Plan IWRS or Manual Documentation Drug Accountability Planning Site Pharmacy Training Monitor Training Trial Master File Planning Site IP Release 12

13 Quality Product On Budget Meets GXP Regulations On Time 13

14 EXAMPLE TRIAL 1: Large Global Study with Home Health Care IV Infusions 14

15 EXAMPLE TRIAL 1 Large Global Study with Home Health Care IV Infusions with HHC Nurse (1) Packaging Design Challenge: Global study in 5 continents Regional Diluent and Placebo Requirements Subject Weight Based Dosing Cost to pack/label many IMP vials, diluent and placebo (1) Global Bulk Kit Solutions: Global Bulk pack IMP only labeled with booklet label including all countries and languages. Kits Not subject specific Allowed for reduced packaging, pick and pack, storage and distribution costs. Flexibility to use the kits in all countries Sites supplied Commercial Diluent and Placebo 15

16 EXAMPLE TRIAL 1 Large Global Study with Home Health Care IV Infusions with HHC Nurse (2) Dose Calculation and Drug Accountability Challenges: Potential manual dose calculation errors (human error) with so many UNBLINDED pharmacists involved Extremely large number of weekly infusions and IMP lots to account for (2) IWRS Dose Calculation and Electronic Accountability Solutions: IWRS was programmed using inputs from the pharmacists to calculate the dose and infusion volume for the UNBLINDED pharmacist for each infusion to mitigate manual dose calculation errors Programmed electronic drug accountability as a central location to access all sites receipt, dispensing, damaged and current inventory by lot number. Allowed for remote real-time unblinded monitor oversight in-between on-site UNBLINDED monitoring visits. Massive amount of data to try to manage by paper. 16

17 EXAMPLE TRIAL 1 Large Global Study with Home Health Care IV Infusions with HHC Nurse (3) Home Infusion Challenge: Weekly infusions for many years, so subjects needed an option to receive infusions at home due to the duration of the study and frequency of the infusions; and have the flexibility to change their plans with short notice IMP must be infused within a few hours of reconstitution (3) IWRS Home Infusion Solution: Train Local Pharmacy sites in the vicinity of subject home for IP preparation Program IWRS with flexible subject infusion location and IMP forecasting 17

18 EXAMPLE TRIAL 2: Global Study with Subject Home Self Administration & Supplies Suitcase 18

19 EXAMPLE TRIAL 2 : Global Study with Subject Home Self Administration & Supplies Suitcase Packaging and Ancillary Supply Challenges: Designing 1 optimal blinded kit to accommodate the following: Multiple treatment arms to cover the max time at home between site dispensing visits Minimize vial overage/waste and be small enough to fit in 2-8C shipper Temperature controlled shippers needed or distribution to subject home Labeling for multiple countries for a small vial Medical device and many ancillary supplies required for daily self-administration Packaging Solution: 2-8C self activated single use shippers for home transportation Optimal kit size to fit the maximum number of vials in the kit and still fit in the self-activated shipper Program IWRS to dispense flexible number of kits per site dispensing visit Serialized blinded carton single panel labels that includes multiple languages and a tear off for accountability Serialized vial wrap around labels due to small vial size Develop stability studies for data to support temperature excursions should they occur at subject home Ancillary supplies subject suitcase 19

20 EXAMPLE TRIAL 2 : Ancillary Supplies Suitcase for Subject Home Administration Uniquely Serialized IMP Kits Ancillary Supplies for IP Preparation and Device Cleaning Medical Device Global Power Adaptor Considerations 20

21 EXAMPLE TRIAL 3 Global Program (2 Protocols) with Short Expiry Date Developmental IMP 21

22 EXAMPLE TRIAL 3 : Global Program (2 Protocols) with Short Expiry Date Developmental IMP Short Expiry Dating Challenges : IMP is a Developmental product where expiry date will be extended throughout the trial. When EXP Date is preprinted on the IMP labels: costs, time and risk incurred with relabeling EXP date when stability data supports an extension Three potential solutions were evaluated (A) IWRS to control expiry (B) JIT Labeling at the point of distribution (C) Printing small and frequent batches New EU regulation (Clinical Trials Regulation EU No 536/2014, April 2014) 22

23 EXAMPLE TRIAL 3 : Global Program (2 Protocols) with Short Expiry Date Developmental IMP Short Expiry Solution A: IWRS to Control Expiry Date in Lieu of Printing Exp Date on Label Document plan for extending expiry date with the EU QP and with the IWR vendor. Seek Regulatory Approval of using IWR to manage expiry dating Include the IMP Stability Study details for extending Exp Date RA submissions Include the intent to use IWR to manage Exp Date in the Protocol and RA Submissions Include IWR QP Declaration in RA submissions. Guidance in the Jan 2009 ISPE/PDA White Paper and the 2011 EMEA Reflection Paper published Dec 2013 Set the IWR Do not Dispense Date for a larger time period than clinic visit window. IWR Dispensing Printout indicates the most current Exp Date and the Site Pharmacist would handwrite the Exp Date on the IMP carton labels at the time of dispensing Subject would be required to return all serialized vials (used and unused) at next clinic visit for full reconciliation along with the printed IWR Dispensing Printout signed by the subject confirming use before Exp Date. IWRS to manage Exp Date in lieu of printing date on IMP labels was evaluated but NOT PURSUED due to low probability of regulatory approval in target countries due to the new Clinical Trials Regulation EU No 536/2014 (April 2014) 23

24 EXAMPLE TRIAL 3 : Global Program (2 Protocols) with Short Expiry Date Developmental IMP Short Expiry Solution B: Just In Time (JIT) Exp Date Labeling at Depot Design Separate Label Stock for US Design Ex-US Label for JIT expiry date EU QPs to approve master JIT batch record template Designed IMP labels with ease of JIT application & relabel extensions in mind JIT Exp Date labeling at depot level at time of dispatch under GMP batch record Short Expiry Solution C: Small Frequent Pack/Label Campaigns Pack/Label small, frequent campaigns with the Exp Date preprinted on IMP labels This approach results in higher pack/label costs but minimizes the IMP stock at the site to relabel or discard when stability data is available to justify an expiry date extension. This approach requires close communication with the study team and close management of IP at the depots and sites to make best guesstimates of quantity to pack/label. 24

25 EXAMPLE TRIAL 3 : Global Program (2 Protocols) with Short Expiry Date Developmental IMP REGULATION (EU) No 536/2014 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 April pdf) EMA Reflection paper on the use of interactive response technologies (interactive voice/web response systems) in clinical trials, with particular emphasis on the handling of expiry dates (Dec 2013) pdf US FDA GMP 21CFR (g) exempts IMP s from the requirement to have use-by dates on IMP labels. ISPE/PDA White Paper: Using An Interactive Voice System or Interactive Web Technology to Manage IMP Retest Dates in Lieu of Placing Retest Dates on IMP labels (Jan-2009 Version 4.0) 25

26 The Art of Clinical Supply Planning : Quality Product in the Right Place at the Right Time Packaging and Labeling IWRS Programming Distribution Setup Regulatory Submission and Approval Pharmacy and Monitor Training FPFV Startup Protocol Design And Forecast Administration and Supplies Investigational Medicinal Product 26

27 Thank you! Questions? 27